High flavivirus structural plasticity demonstrated by a non-spherical morphological variant
Seamus R. Morrone, Valerie S. Y. Chew, Xin-Ni Lim, Thiam‐Seng Ng, V.A. Kostyuchenko, Shuijun Zhang, Melissa Wirawan, Pau-Ling Chew, Jaime Lee, Joanne L. Tan, Jiaqi Wang, Ter Yong Tan, Jian Shi, Gavin Screaton, Marc C. Morais, Shee‐Mei Lok
Abstract
Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to ~10 Å resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.